Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/87083
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Type: Journal article
Title: Transcriptomic and biochemical analyses identify a family of chlorhexidine efflux proteins
Author: Hassan, K.
Jackson, S.
Penesyan, A.
Patching, S.
Tetu, S.
Eijkelkamp, B.
Brown, M.
Henderson, P.
Paulsen, I.
Citation: Proceedings of the National Academy of Sciences of the United States of America, 2013; 110(50):20254-20259
Publisher: National Academy of Sciences
Issue Date: 2013
ISSN: 0027-8424
1091-6490
Statement of
Responsibility: 
Karl A. Hassan, Scott M. Jackson, Anahit Penesyan, Simon G. Patching, Sasha G. Tetu, Bart A. Eijkelkamp, Melissa H. Brown, Peter J. F. Henderson, and Ian. T. Paulsen
Abstract: Chlorhexidine is widely used as an antiseptic or disinfectant in both hospital and community settings. A number of bacterial species display resistance to this membrane-active biocide. We examined the transcriptomic response of a representative nosocomial human pathogen, Acinetobacter baumannii, to chlorhexidine to identify the primary chlorhexidine resistance elements. The most highly up-regulated genes encoded components of a major multidrug efflux system, AdeAB. The next most highly overexpressed gene under chlorhexidine stress was annotated as encoding a hypothetical protein, named here as AceI. Orthologs of the aceI gene are conserved within the genomes of a broad range of proteobacterial species. Expression of aceI or its orthologs from several other γ- or β-proteobacterial species in Escherichia coli resulted in significant increases in resistance to chlorhexidine. Additionally, disruption of the aceI ortholog in Acinetobacter baylyi rendered it more susceptible to chlorhexidine. The AceI protein was localized to the membrane after overexpression in E. coli. This protein was purified, and binding assays demonstrated direct and specific interactions between AceI and chlorhexidine. Transport assays using [(14)C]-chlorhexidine determined that AceI was able to mediate the energy-dependent efflux of chlorhexidine. An E15Q AceI mutant with a mutation in a conserved acidic residue, although unable to mediate chlorhexidine resistance and transport, was still able to bind chlorhexidine. Taken together, these data are consistent with AceI being an active chlorhexidine efflux protein and the founding member of a family of bacterial drug efflux transporters.
Keywords: Drug resistance; membrane transport; opportunistic pathogen
Rights: Copyright status unknown
RMID: 0030012717
DOI: 10.1073/pnas.1317052110
Grant ID: http://purl.org/au-research/grants/nhmrc/535053
http://purl.org/au-research/grants/arc/DP110102680
Appears in Collections:Molecular and Biomedical Science publications

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